Ulcerated Atrophic Striae from Etretinate Paul H

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Ulcerated Atrophic Striae from Etretinate Paul H. Bowman, MD, Shreveport, Louisiana Daniel J. Hogan, MD, Shreveport, Louisiana

Oral retinoids such as etretinate and acitretin are commonly associated with dose-dependent, mu- cocutaneous side effects such as dryness, peel- ing, and fragility. Although these effects can be ex- treme in some patients and even require discontinuation of treatment, thinning of skin to the point of atrophy and ulceration has never been reported in the English literature. We present the case of a patient with psoriasis in whom ulcerated atrophic striae developed during etretinate therapy. After discontinuation of etretinate, all cutaneous ulcers resolved. Subsequently, the patient had a favorable response to oral calcitriol (1,25-di- hydroxy vitamin D3), a novel therapy for psoriasis.

ral synthetic retinoids are used in the treatment of a variety of proliferative and hyper- O keratotic skin disorders. Dose-related side effects are common, and include cheilitis, palmar- plantar desquamation, conjunctivitis, hair loss, and nail changes. Skin fragility is a well-documented side effect of etretinate, an aromatic retinoid, and often limits its use. Blistering and frank ulceration are un- common and have rarely been reported.1,2 We present a case of ulceration of atrophic striae in a patient receiving etretinate. To our knowledge, this is the first FIGURE 1. Shallow ulcerations developed within pre- 3 such case to appear in the English literature. existing striae of the left arm. Case Report A 29-year-old black man with acquired immunodefi- Cultures from the abscess grew methacillin-sensitive ciency syndrome (CD4 count 1, human immunodefi- Staphylococcus aureus, and the patient gradually im- ciency virus-1 RNA viral load 396,152 copies), hepa- proved with intravenous antibiotics. The patient’s titis B, glucose-6-phosphate dehydrogenase deficiency, psoriasis worsened, despite continued treatment with and a 3-year history of psoriasis was admitted to the 0.1% triamcinolone ointment. The patient denied hospital for work-up of fever and perirectal abscess. prior systemic corticosteroid treatment and stated that stretch marks had appeared within the last year in ar- Dr. Bowman is a Dermatology Fellow with Louisiana State eas where he had not applied topical corticosteroids. University at Shreveport, Overton Brooks Veterans Administration Prior to their development, he had taken etretinate Medical Center, Shreveport, Louisiana, where Dr. Hogan is a pro- for several months, but had discontinued it 6 months fessor and Chief of Dermatology. REPRINT REQUESTS to Louisiana State University Medical Center, before admission. Section of Dermatology, 1501 Kings Highway, Shreveport, Physical examination revealed a thin, chroni- Louisiana 71130-3932 (Dr. Hogan). cally ill-appearing black man with extensive plaque-

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type psoriasis covering most of his body. We noted atic skin. Measurement of Ki67 protein showed a multiple atrophic striae extending from the axillae 62% decrease in keratinocyte proliferation.5 In- to the inner flexor aspects of the biceps, and on the creased corneocyte desquamation and near-elimina- flanks bilaterally. tion of the stratum corneum were believed to be the Liver function tests and random cortisol gave main cause of skin fragility. normal results. We discontinued the triamcinolone Cutaneous ulceration, although rare, is important ointment, and initiated treatment with etretinate, to recognize as a side effect of etretinate therapy. 25 mg daily, and 0.005% calcipotriene ointment to Skin fragility is dose related, but our patient expe- psoriatic plaques twice daily. The patient improved rienced ulceration while on the low dose of 0.3 somewhat, but after 2 weeks, several shallow ulcers mg/kg daily, compared with 1 mg/kg in the only pre- developed within the striae on his left arm (Figure viously reported case.3 Fortunately, we were able to 1), which were treated with 1% silver sulfadiazine discontinue the drug early and avoid potential ex- twice daily. Porphyrin screen, anti-streptolysin O tensive ulceration and possible secondary infection titer, and viral culture of the ulcer were negative. in this immunocompromised patient. No further ulcers appeared after discontinuation of Oral calcitriol (1,25-dihydroxyvitamin D3), a the etretinate, but the psoriasis became erythroder- novel therapy for refractory psoriasis, was very useful mic within several days. After a 24-hour urine test in our patient. Oral calcitriol inhibits proliferation of revealed normal calcium excretion, the cal- epidermal cells in a dose-dependent fashion, and in- cipotriene ointment was discontinued and he began duces terminal differentiation. Smith et al6 showed treatment with 0.25 mg calcitriol daily. The patient’s these effects in keratinocytes cultured from patients psoriasis markedly improved, and the cutaneous ul- with psoriasis, and documented clinical efficacy of cers resolved. oral calcitriol as monotherapy.

Comments REFERENCES Increased skin fragility is common in patients 1. Ramsay B, Bloxham C, Eldred A, et al: Blistering, erosions treated with oral retinoids, but frank cutaneous ul- and scarring in a patient on etretinate. Br J Dermatol 121: ceration is rare. Initially, it was thought that skin 397-400, 1989. fragility was due to mucous metaplasia (“de-differ- 2. Neild VS, Moss RF, Marsden RA, et al: Retinoid-induced entiation”) of keratinocytes, resulting in an anti- skin fragility in a patient with hepatic disease. Clin Exp Der- keratinizing effect. It was also suggested that fragility matol 10: 459-465, 1985. resulted from altered dermal connective tissue, since 3. Bordier C, Flechet ML, Thomine E, et al: Rupture de ver- vitamin A affects acid mucopolysaccharide synthe- getures au cours d’un psoriasis pustuleux traite par etretinate sis, and in pharmacologic quantities can stimulate (Tigason). Ann Dermatol Venereol 111: 929-931, 1984. breakdown of connective tissue. One study chal- 4. Williams ML, Elias PM: Nature of skin fragility in patients lenged this idea when it reported normal urinary hy- receiving retinoids for systemic effect. Arch Dermatol 117: droxyproline excretion (an index of collagen catab- 611-619, 1981. olism) in patients with retinoid-induced skin 5. Gottlieb SL, Hayes E, Gilleaudeau P, et al: Cellular action fragility.4 The authors attributed skin fragility to ac- of etretinate in psoriasis: enhanced epidermal differentiation tive shedding of desmosomes in the stratum spinu- and reduced cell-mediated inflammation are unexpected losum and accumulations of amorphous material outcomes. J Cutan Pathol 23: 404-418, 1996. both intracellularly and extracellularly. A more re- 6. Smith EL, Pincus SH, Donovan L, et al: A novel approach cent study found enhancement of cellular differen- for the evaluation and treatment of psoriasis. J Am Acad Der- tiation and disappearance of parakeratosis in psori- matol 19: 516-528, 1988.

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